{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:59:04Z","timestamp":1792641544140,"version":"4.5.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,3,28]]},"abstract":"<jats:p>\n                    Motor incoordination, immune deficiencies, and an increased risk of cancer are the characteristic features of the hereditary disease ataxia\u2013telangiectasia (A-T), which is caused by mutations in the\n                    <jats:italic>ATM<\/jats:italic>\n                    gene. Through gene targeting, we have generated a line of\n                    <jats:italic>Atm<\/jats:italic>\n                    mutant mice,\n                    <jats:italic>Atm<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>y\/y<\/jats:italic>\n                    <\/jats:sup>\n                    mice. In contrast to other\n                    <jats:italic>Atm<\/jats:italic>\n                    mutant mice,\n                    <jats:italic>Atm<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>y\/y<\/jats:italic>\n                    <\/jats:sup>\n                    mice show a lower incidence of thymic lymphoma and survive beyond a few months of age.\n                    <jats:italic>Atm<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>y\/y<\/jats:italic>\n                    <\/jats:sup>\n                    mice exhibit deficits in motor learning indicative of cerebellar dysfunction. Even though we found no gross cerebellar degeneration in older\n                    <jats:italic>Atm<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>y\/y<\/jats:italic>\n                    <\/jats:sup>\n                    animals, ectopic and abnormally differentiated Purkinje cells were apparent in mutant mice of all ages. These findings establish that some neuropathological abnormalities seen in A-T patients also are present in\n                    <jats:italic>Atm<\/jats:italic>\n                    mutant mice. In addition, we report a previously unrecognized effect of\n                    <jats:italic>Atm<\/jats:italic>\n                    deficiency on development or maintenance of CD4\n                    <jats:sup>+<\/jats:sup>\n                    8\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes. We discuss these findings in the context of the hypothesis that abnormal development of Purkinje cells and lymphocytes contributes to the pathogenesis of A-T.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.7.3336","type":"journal-article","created":{"date-parts":[[2012,7,25]],"date-time":"2012-07-25T13:37:36Z","timestamp":1343223456000},"page":"3336-3341","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":169,"title":["Abnormal development of Purkinje cells and lymphocytes in\n                    <i>Atm<\/i>\n                    mutant mice"],"prefix":"10.1073","volume":"97","author":[{"given":"Paul R.","family":"Borghesani","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology and Division of Cellular and Molecular Biology, Dana\u2013Farber Cancer Institute; Howard Hughes Medical Institute and The Children's Hospital; The Center for Blood Research; Departments of Neurobiology and Genetics, Harvard 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